Methods and achievements in experimental pathology最新文献

During the healing of an open wound, the majority of granulation tissue fibroblasts (myofibroblasts) acquire morphological, biochemical, pharmacological, and immunological characteristics typical of contractile cells. The presence of contractile proteins and the appearance of gap junctions between several myofibroblasts make them similar to cultivated fibroblasts; these have been proven to develop in vitro a contractile force similar to that exerted by granulation tissue during wound contraction. These observations suggest that myofibroblasts are responsible for granulation tissue contraction. Epidermal cells moving over an open wound also develop a contractile apparatus and many cellular connections in the form of gap junctions. These changes may be the morphological support for epithelial cell movements. The presence of gap junctions between myofibroblasts and healing epidermal cells shows that granulation tissue contraction and epithelial cell movement are probably synchronized rather than individual phenomena.

Methods are described for maintaining hypophysectomized rats (model for panhypopituitarism). Prolactin-secreting pituitary tumors can be induced in rats or mice by administration of estrogens; thyroid stimulating hormone-secreting tumors will occur in some mice after thyroid ablation by radioactive iodine. Estrogens in hamsters usually produce intermediate lobe tumors of the pituitary associated with hypothalamic degeneration. Sex hormone-secreting adrenal tumors can follow surgical gonadectomy in mice. Spontaneous corticoid-secreting adrenal tumors may occur spontaneously in Osborne-Mendel rats. Secretory gonadal tumors have been induced by transplantation of a gonad into the spleen of a gonadectomized host. Both secretory and non-secretory ovarian tumors can be produced by irradiation or chemical carcinogens in mice. In some mice, secretory testicular tumors can be produced by estrogen administration. Thyroid tumors can be induced in rodents by various kinds of goitrogens and irradiation. Parathyroid hyperplasia may occur with spontaneous renal disease in rats. A syndrome simulating diabetes mellitus can occur in rare strains of mice or can be induced by chemical destruction of the islets of Langerhans with alloxan.

Congenitally athymic nude mice (nu/nu) are presented as a model for the study of cell-mediated immunologic deficiencies. These mice possess a vestigial thymus which is incapable of producing mature T-cells as shown by a decreased lymphocyte population carrying the theta antigen and depleted 'thymus-dependent' areas in their peripheral lymphoid organs. However, they have T-cell precursors in their bone marrow. Nude mice lack 'thymosin', a thymic factor secreted by the epithelial cells of the thymus. They also have impaired T-cell functions as demonstrated by an absence of delayed hypersensitivity reactions, an inability to reject skin allografts and a decreased antibody response to some T-dependent antigens. But their response to T-independent antigens is normal. The presence of circulating auto-antibodies and immune-complex type glomerulonephritis in nude mice reinforces the hypothesis that spontaneous autoimmunity and B-cell hyperactivity are associated with T-cell deficiency. On the other hand, they are not especially susceptible to spontaneous tumor development. Correlations are made between the pathologic findings in nude mice and some congenital cellular immunologic disorders in man.

Nutritional secondary hyperparathyroidism (NSH) defines a spontaneous and experimental disease in most domesticated and in some wild animals, caused by dietary calcium deficiency and/or phosphorus excess. Calcium deficiency results directly in hypocalcemia, and phosphorus excess induces hyperphosphatemia which causes hypocalcemia. Secondary hyperparathyroidism thus results and the plasma parameters return to normal and are maintained but only at the expense of progressive bone loss. The bone loss is generalized but the bones are not uniformly affected. The hierarchy of bone loss is, in decreasing order, the jaw bones, especially the alveolar bone, other skull bones, ribs, vertebrae and, finally, long bones. Osteocytic osteolysis is the main mechanism of resorption and application of this concept is a condition sine qua non in the interpretation of the histologic lesions. The early loss of alveolar bone constitutes the initial event in periodontal disease in animals. The osseous lesions in animal NSH are reversible by correction of dietary calcium and phosphorus levels, provided a hyperostotic osteodystrophia fibrosa has not yet developed. The applicability of animal NSH as a model for human osteopenic conditions, including periodontal disease and spinal osteoporosis, is supported by the very inadequate calcium and phosphorus nutrition in most Western countries. The diet is deficient in calcium and excessive in phosphorus; both conditions induce NSH in animals. The degree of dietary calcium deficiency, as influenced by geographic, economic, and social factors, is positively correlated to the degree of periodontal disease and osteoporosis in the population. Evidence is presented to show that the radiographic and histologic manifestations of human periodontal disease and osteoporosis are the same as those of animal NSH. Periodontal disease is therefore considered a fore-runner to the clinically more important spinal osteoporosis. Limited experiments in human periodontal disease indicate that added dietary calcium can positively influence the alveolar bone loss.

Traditional approaches to human and experimental teratology are briefly described, with roles of pathologists indicated. Some approaches to experimental teratology which pathologists might use are then described and illustrated. These include identification of subclasses of malformation types, study of the chronologic sequence of maldevelopment, study of embryo death, and examination of tumor-malformation relationships. The malformations used to illustrate these approaches are cleft palate, anencephaly, hydrocephalus, and intestinal atresia. The final section deals with general methodology in experimental teratology; a listing of books dealing with experimental teratology is included.

The use of animal models in the experimental production of liver diseases similar to those of man is still in its infancy. There is a need to discover new models more closely related to counterpart syndromes in man in the fields of hepatorenal syndrome, neonatal jaundice, Wilson's disease, cholelithiasis, viral hepatitis, biliary atresia, and cirrhosis, to mention only a few. With the continued indiscriminate inbreeding of companion animals as well as the planned inbreeding of laboratory animals, there is little doubt that many more will soon be available. The current availability of mutant rats and sheep with bilirubin transport defects has allowed for a better understanding of how organic anions are transported by the liver. Many other currently available experimental animal models herein briefly reviewed have been only superficially studied. It is the intent of this chapter to provide for post-doctoral students an appreciation for the many animal model systems available for experimental hepatic research.

The mode of pathological reaction of the skeletal muscle fibres to injury is now well understood as a result of the large number of experimental studies and the wide variety of techniques applied to the problem, as recounted above. The most notable aspect of the reaction of the injured muscle fibre is the remarkable stereotyped character of the resulting changes as demonstrated by many diverse agents producing surprisingly similar results. The initial lesion is essentially local coagulative necrosis of the muscle fibre. If the animal survies, such necrosis is inevitably followed by a series of biological reactions inherent in muscle and which lead to the removal of dbris and the proliferation of myoblasts...

We have been concerned in the first section of this review with those diseases that are aging processes, or appear to be so. Some of these (e.g., cardiovascular, pulmonary, neoplasia) cause the death of a large proportion of animals, while others (e.g., osteoporosis, amyloidosis), though clearly progressive with age, are nonfatal. Many diverse factors influence the normal process of aging. Restriction of dietary caloric intake prolongs lifespan and decreases the incidence and severity of diseases associated with aging, probably by depressing anterior pituitary gland function...

The oral administration to guinea-pigs of an aqueous solution of carrageenan derived from the red seaweed, Eucheuma spinosum, provides a useful, readily available experimental model for the study of ulcerative disease of the colon. Two types of ulcerative disease can be produced within a 4-6 week period, viz., ulceration localised mainly to the caecum by using 1% undegraded carrageenan in the drinking fluid, and extensive ulceration involving caecum, colon, and rectum by using 5% degraded carrageenan. Ulceration is probably due to the local action of carrageenan in the bowel.